The long term goal of this proposal is to study signaling in the context of transformed cells and how transformed cells switch to a more aggressive phenotype. The study will focus on the pleiotrophin (PTN) signaling pathway which has been shown to transform cells and initiate angiogenesis. Much of the initial work will be to find interactive proteins with the cytoplasmic domain of the transmembrane tyrosine phosphatase, receptor protein tyrosine phosphatase (RPTP) beta/zeta. Following the identification of these proteins, their roles as downstream elements of this pathway will be characterized. The major aim of this proposal is to identify characterize the role of proteins interactive with the cytoplasmic domain of RPTP beta/zeta in promoting the PTN signal. If time and effort permit, I plan to seek the specific sites in beta-catenin that have increased tyrosine phosphorylation in PTN-stimulated cells.